Comparison of the Fecal Microbiome in Identical Twins Discordant for Colon Polyps

描述（由申请人提供）：CRC由腺瘤性和锯齿状结肠息肉引起，可通过结肠镜检查识别。几项研究已经报道了粪便或结肠粘膜中的微生物群组成与CRC之间的关联。这些研究通常规模较小，并且没有控制宿主基因型或儿童早期暴露，这是设定肠道微生物群的两个最有影响力的因素。我们建议通过比较45对结肠息肉病史不一致的单卵（MZ）双胞胎中的微生物群多样性和分类群来确定肠道微生物群与结肠息肉之间的关联。使用息肉不和谐的MZ双胞胎作为受试者是一个优势，因为幼儿环境和遗传因素都得到了控制。从加州双胞胎项目招募的双胞胎将收集粪便样本，并通过邮寄的方式将粪便样本放入我们提供的标本管中，连同饮食问卷、生活方式和暴露问卷、签名的HIPAA表格（允许收集验证息肉和结肠镜检查的医疗记录）和签名的知情同意书一起沿着寄回。根据先前对淋巴瘤不一致双胞胎中微生物群的研究，我们预计依从率为70%。微生物多样性和分类群将在马里兰州大学基因组科学研究所的国际微生物组专家Jacques Ravel博士的实验室中使用150 mg粪便的16 rs测序来确定。Ravel博士的团队将进行DNA测序分析和生物信息学，并提供微生物群多样性指标（香农指数作为衡量人内差异或α多样性的指标，Unifrac用于衡量人与人之间的差异或β多样性）。将使用QIIME和其他标准软件对物种水平进行分类。我们将使用条件logistic回归框架来研究有和没有结肠息肉的MZ双胞胎之间肠道微生物组多样性和特定细菌种类的差异。增加1个单位（即生物标志物增加1个SD）的最小可检测比值比为1.86（<$= 0.05）和2.48（<$= 0.002），这与我们在13个淋巴瘤不一致对的初步研究中观察到的微生物群差异相似（外推至OR的平均差异）。这项初步研究的意义在于有可能证明肠道微生物群与结肠息肉之间的关系，而与宿主基因型或儿童早期暴露无关。

DESCRIPTION (provided by applicant): CRC arises from adenomatous and serrated colon polyps that are identifiable with colonoscopy. Several studies have reported an association between microbiota composition in feces or colonic mucosa, and CRC. These studies were generally small and did not control for host genotype or early childhood exposures, the two most influential factors in setting the gut microbiota. We propose to determine the association between the gut microbiota and colon polyps by comparing microbiota diversity and taxa in 45 monozygotic (MZ) twin pairs discordant for a history of colon polyps. Using polyp-discordant MZ twins as subjects is an advantage because both early childhood environment and genetic factors are controlled. Twins recruited from the California Twin Program will collect and return stool samples in specimen tubes that we provide, along with a diet questionnaire, lifestyle and exposure questionnaire, a signed HIPAA form to allow collection of medical records verifying the polyps and colonoscopy, and a signed informed consent, by mail. Based on a previous study of microbiota in lymphoma-discordant twins, we expect a 70% compliance rate. Microbiota diversity and taxa will be determined using 16rs sequencing of 150 mg of stool in the laboratory of Dr. Jacques Ravel, an international microbiome expert at the University of Maryland's Institute for Genome Sciences. Dr. Ravel's team will perform the DNA sequencing assays and bioinformatics and provide microbiota measures of diversity (Shannon's index as a measure of within person differences or alpha diversity, and Unifrac to measure between-person differences, or beta diversity). Taxonomic classification to the species level will be performed using QIIME and other standard software. We will use a conditional logistic regression framework to investigate the difference in gut microbiome diversity and specific bacterial species between MZ twins with and without colon polyps. The minimum detectable odds ratio for a 1 unit increase (i.e. a 1 SD increase in the biomarker) is 1.86 (¿ = 0.05) and 2.48 (¿ = 0.002), which is similar to the microbiota differences observed in our pilot study of 13 lymphoma-discordant pairs (mean differences extrapolated to an OR). The significance of this pilot study lies in the potential to demonstrate a relationship between the gut microbiota and colon polyps independent of host genotype or early childhood exposures.